Human adipose ECM alleviates radiation-induced skin fibrosis via endothelial cell-mediated M2 macrophage polarization

Chinnapaka, Somaiah; Yang, Katherine S.; Surucu, Yusuf; Bengur, Fuat B.; Arellano, José A.; Tirmizi, Zayaan; Malekzadeh, Hamid; Epperly, Michael W.; Hou, Wen; Greenberger, Joel S.; Rubin, J. Peter; Ejaz, Asim

doi:10.1016/j.isci.2023.107660

Cited by 6 publications

(2 citation statements)

References 54 publications

(88 reference statements)

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“…A recent model explored the effect of adipose tissue-derived ECM (Ad-ECM) for treating radiation-induced skin fibrosis [61]. Ad-ECM treatment reduced proinflammatory and fibrotic gene expression and increased anti-inflammatory cytokines and bone marrow cell migration.…”

Section: Discussionmentioning

confidence: 99%

Exploring Anti-Fibrotic Effects of Adipose-Derived Stem Cells: Transcriptome Analysis upon Fibrotic, Inflammatory, and Hypoxic Conditioning

Frommer,

Langridge,

Beedie

et al. 2024

Cells

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Autologous fat transfers show promise in treating fibrotic skin diseases, reversing scarring and stiffness, and improving quality of life. Adipose-derived stem cells (ADSCs) within these grafts are believed to be crucial for this effect, particularly their secreted factors, though the specific mechanisms remain unclear. This study investigates transcriptomic changes in ADSCs after in vitro fibrotic, inflammatory, and hypoxic conditioning. High-throughput gene expression assays were conducted on ADSCs exposed to IL1-β, TGF-β1, and hypoxia and in media with fetal bovine serum (FBS). Flow cytometry characterized the ADSCs. RNA-Seq analysis revealed distinct gene expression patterns between the conditions. FBS upregulated pathways were related to the cell cycle, replication, wound healing, and ossification. IL1-β induced immunomodulatory pathways, including granulocyte chemotaxis and cytokine production. TGF-β1 treatment upregulated wound healing and muscle tissue development pathways. Hypoxia led to the downregulation of mitochondria and cellular activity.

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Section: Discussionmentioning

confidence: 99%

Exploring Anti-Fibrotic Effects of Adipose-Derived Stem Cells: Transcriptome Analysis upon Fibrotic, Inflammatory, and Hypoxic Conditioning

Frommer,

Langridge,

Beedie

et al. 2024

Cells

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“…Moreover, the impaired DNA may cause uncontrolled and abnormal replication and proliferation, disturbing the normal cell proliferative phase of wound healing . After days and months of radiation, acute RISI wounds will be transformed into chronic wounds, and the accumulation of inflammatory cells and tissue damage eventually leads to severe tissue destruction and the disorder of the inflammatory microenvironment. − More importantly, the inflammatory signals can prompt fibroblasts to differentiate into myofibroblasts, leading to excessive ECM deposition and ultimately causing skin fibrosis formation. , Studies have shown that upregulation of anti-inflammatory cytokines and promotion of M2 macrophage polarization can effectively alleviate RISI chronic symptoms. , …”

Section: Introductionmentioning

confidence: 99%

Multifunctional Glycopeptide-Based Hydrogel via Dual-Modulation for the Prevention and Repair of Radiation-Induced Skin Injury

Guo,

Zhang,

Mao

et al. 2024

ACS Biomater. Sci. Eng.

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The radiation-induced skin injury (RISI) remains a great challenge for clinical wound management and care after radiotherapy, as patients will suffer from the acute radiation injury and long-term chronic inflammatory damage during the treatment. The excessive ROS in the early acute stage and prolonged inflammatory response in the late healing process always hinder therapeutic efficiency. Herein, we developed an extracellular matrix (ECM)-mimetic multifunctional glycopeptide hydrogel (oCP@ As) to promote and accelerate RISI repair via a dual-modulation strategy in different healing stages. The oCP@As hydrogel not only can form an ECM-like nanofiber structure through the Schiff base reaction but also exhibits ROS scavenging and DNA doublestrand break repair abilities, which can effectively reduce the acute radiation damage. Meanwhile, the introduction of oxidized chondroitin sulfate, which is the ECM polysaccharide-like component, enables regulation of the inflammatory response by adsorption of inflammatory factors, accelerating the repair of chronic inflammatory injury. The animal experiments demonstrated that oCP@As can significantly weaken RISI symptoms, promote epidermal tissue regeneration and angiogenesis, and reduce pro-inflammatory cytokine expression. Therefore, this multifunctional glycopeptide hydrogel dressing can effectively attenuate RISI symptoms and promote RISI healing, showing great potential for clinical applications in radiotherapy protection and repair.

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Identification and Management of Radiation Late Effects in Humans

Greenberger

2024

Radiation Oncology and Radiation Biology

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Human adipose ECM alleviates radiation-induced skin fibrosis via endothelial cell-mediated M2 macrophage polarization

Cited by 6 publications

References 54 publications

Exploring Anti-Fibrotic Effects of Adipose-Derived Stem Cells: Transcriptome Analysis upon Fibrotic, Inflammatory, and Hypoxic Conditioning

Exploring Anti-Fibrotic Effects of Adipose-Derived Stem Cells: Transcriptome Analysis upon Fibrotic, Inflammatory, and Hypoxic Conditioning

Multifunctional Glycopeptide-Based Hydrogel via Dual-Modulation for the Prevention and Repair of Radiation-Induced Skin Injury

Identification and Management of Radiation Late Effects in Humans

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